The broad goal of this laboratory is to understand, at the cellular level, the neurophysiological basis for maturation of respiratory control. The opossum (Didelphis marsupialis), a marsupial mammal, is being used as the developmental model. The objective in this application is to investigate possible mechanisms underlying the very brief inspiration in immature suckling opossums. Previous results in sucklings showed very few medullary inspiratory neuronal action potentials associated with the inspired breath; it was also inferred that phasic activity from lung mechanoreceptors would have little effect on the inspired breath. Specific protocols will determine the following: 1) whether a strategy to avoid fatigue of neuronal discharge limits the inspired breath; 2) whether increased responsiveness of inspiratory cells to inhibitory neurotransmitters limits the inspired breath and, 3) whether tonic discharge from lung mechanoreceptors limits the inspired breath. Studies will be performed on animals from about two postnatal weeks of age to the adult stage. Animals will be anesthetized with the barbiturate derivative, Inactin, and paralyzed where necessary with pancuronium. Methods to be utilized include extracellular recordings from medullary neurons which discharge with inspiration, recording respiratory muscle or phrenic nerve activity, application of excitatory and inhibitory amino acids as-well as their agonists and antagonists near recorded cells, antidromic spinal cord stimulation of medullary neurons; vagal stimulation and administration of hypercapnic and asphyxiant test gases. The studies in this application are of importance because human infants are now surviving increasingly premature births, and knowledge of the limitations imposed on regulation of breathing by the immature nervous system is very much needed. Apneas of prematurity and sudden infant death syndrome are two problems which are likely related to immaturity of, or defective maturation of, the central nervous system.